Abstract
Mitochondrial permeability transition pore (mPTP) is a complex consists of multiple proteins; adenine nucleotide translocator (ANT) in the mitochondrial inner membrane, cyclophilin D (CypD) in the matrix, and the voltage - dependent anion channel (VDAC) in the mitochondrial outer membrane. Mitochondria take up Ca²⁺ via Ca²⁺ uniporters. When Ca²⁺ loading within mitochondrial matrix exceeds over their capacity, mPTP opens. The opening of mPTP is induced by binding of CypD and ANT. Deletion of CypD in mice enhanced mitochondrial Ca²⁺ uptake and improved symptoms of model animals of neurodegenerative diseases. In many types of animal models of neurodegenerative diseases, increased immobility time was obser ved in forced swimming test and tail suspension test. Additionally, patients with neurodegenerative diseases show a high prevalence of depressive symptoms and suicidal attempts. Thus, inhibition of mPTP opening will be a promising candidate for anti- depression treatment. These findings suggest that mPTP inhibitors might be promising as new therapeutic agents for depressive symptoms.
